Desvenlafaxine (O-desmethylvenlafaxine or ODV) is a selective serotonin and norepinephrine reuptake inhibitor (SNRI), is indicated for the treatment of major depressive disorder (MDD). Chemically desvenlafaxine is RS-4-[2-dimethylamino-1-(1-hydroxycyclohexyl)ethyl]phenol of formula I.

Desvenlafaxine is marketed as PRISTIQ® in the form of extended-release tablet for oral administration that contains desvenlafaxine succinate, a structurally novel SNRI for the treatment of MDD. Desvenlafaxine is the major active metabolite of the antidepressant venlafaxine, a medication used to treat major depressive, generalized anxiety, social anxiety and panic disorders. Desvenlafaxine succinate is a white to off-white powder that is soluble in water. The solubility of desvenlafaxine succinate is pH dependent (solubility increases at lower pH). Its octanol:aqueous system (at pH 7.0) partition coefficient is 0.21 & pKa values are 8.34 (dimethylamino group) and 10.11 (phenolic group).
Desvenlafaxine was disclosed by Klamerus, K. J. et al., “Introduction of the Composite Parameter to the Pharmacokinetics of Venlafaxine and its Active O-Desmethyl Metabolite”, J. Clin. Pharmacol. 32:716-724 (1992), U.S. Pat. No. 4,535,186, and as a free base in International Patent Publication No. WO 00/32555. In U.S. Pat. No. 6,673,838, ODV has been incorporated into an extended release tablet, which allegedly reduces adverse effects such as nausea, vomiting, diarrhea, and abdominal pain. The '838 patent discloses the use of hydroxypropylmethyl cellulose (HPMC) alone as a polymer to provide extended release of desvenlafaxine. However, it is known with the art that HPMC matrices may exhibit an initial burst release for soluble drugs and this behaviour has been attributed to the rapid dissolution of the drug from the surface and near the surface of the matrix.
Prior arts describing various controlled release formulation for desvenlafaxine includes U.S. Pat. Nos. 7,291,347; 6,274,171; US Application Nos. 20060193911; 20060193912; 20050175698; 20060193912; 20050244498; 20100209489; 20100330172; EP Publication Nos. 1864967; 1360169; 1711167; 2119696; 2211847 and WO Publication Nos. 2009049354; 2002064543; 2003103603; 2010090991; 2009049354.
Several attempts to provide dosage forms for delivery of desvenlafaxine or salts thereof for extended periods of time have been described previously. However, there still exists a need to develop effective modified release dosage form compositions particularly comprising desvenlafaxine or salts thereof with reduced side effects which can provide sustained delivery of desvenlafaxine or salts thereof, that are easier to manufacture, and involves a low formulation cost. Desvenlafaxine is a weakly basic drug having relatively good solubility at gastric pH and poor solubility at intestinal pH. Thus, formulating Desvenlafaxine or salts thereof into a modified release dosage form that overcomes the solubility issues of desvenlafaxine in the GIT presents a number of problems. Clearly, there is a need for improved compositions providing modified release dosage form that overcomes the solubility issues of desvenlafaxine in the GIT and provide a sustained drug release over the desired period of time to achieve the desired concentration of desvenlafaxine or salts thereof in the blood.